Research Laboratory of Bioresources, Integrative Biology and Valorization LR14ES06, Higher Institute of Biotechnology of Monastir, University of Monastir, Avenue Tahar Haaadded, BP 74, Monastir 5000, Tunisia.
Department of Pathology, Habib Bourguiba University Hospital, Medenine 4100, Tunisia.
Genes (Basel). 2023 Jul 19;14(7):1467. doi: 10.3390/genes14071467.
Genetic and epigenetic modifications present a major cause of relapse and treatment failure in colorectal cancer. This study aims to appreciate the prognostic and predictive value of ERRC1 and MGMT methylation. We also studied the prognostic impact of the ERCC1 rs11615 polymorphism as well as its expression. Methylation profiles of ERCC1 and MGMT were tested by methylation-specific PCR. A polymorphism of ERCC1 was studied using PCR-RFLP and its expression was examined by immunohistochemistry. ERCC1 was methylated in 44.6% of colorectal adenocarcinoma while MGMT was methylated in 69% of cases. MGMT methylation was strongly associated with lymph node metastasis, lymph invasion, venous invasion, perineural invasion, distant metastasis and relapse. Patients with methylation of both genes were more likely to have a poor prognosis and display chemoresistance. IHC analysis revealed that ERCC1 staining was noted in 52.8% of colorectal adenocarcinoma and inversely related to distant metastasis and cancer recurrence. Kaplan Meier analysis revealed that the worst overall survival was significantly associated with ERCC1 and MGMT methylation while decreased ERCC1 expression and T/T genotype exhibited the best overall survival. The methylation of MGMT, alone or combined with ERCC1, is predictive for poor prognosis, short overall survival and chemotherapy response in colorectal cancer.
遗传和表观遗传修饰是结直肠癌复发和治疗失败的主要原因。本研究旨在评估 ERRC1 和 MGMT 甲基化的预后和预测价值。我们还研究了 ERCC1 rs11615 多态性及其表达的预后影响。通过甲基化特异性 PCR 检测 ERCC1 和 MGMT 的甲基化谱。使用 PCR-RFLP 研究 ERCC1 的多态性，并用免疫组织化学检查其表达。44.6%的结直肠腺癌存在 ERCC1 甲基化，而 69%的病例存在 MGMT 甲基化。MGMT 甲基化与淋巴结转移、淋巴浸润、静脉浸润、神经周围浸润、远处转移和复发密切相关。两个基因均甲基化的患者更有可能预后不良且表现出化疗耐药性。免疫组化分析显示，52.8%的结直肠腺癌存在 ERCC1 染色，与远处转移和癌症复发呈负相关。Kaplan-Meier 分析显示，总生存最差与 ERCC1 和 MGMT 甲基化显著相关，而 ERCC1 表达降低和 T/T 基因型则表现出最佳的总生存。MGMT 单独或与 ERCC1 联合甲基化可预测结直肠癌预后不良、总生存期短和化疗反应。
